AIM To study the genetic alteration in ACF andto define the possibility that ACF may be a veryearly morphological lesion with molecularchanges, and to explore the relationshipbetween ACF and colorectal adenoma evencar...AIM To study the genetic alteration in ACF andto define the possibility that ACF may be a veryearly morphological lesion with molecularchanges, and to explore the relationshipbetween ACF and colorectal adenoma evencarcinoma.METHODS DNA from 35 CRC, 15 adenomas, 34ACF and 10 normal mucus was isolated by meansof microdissection. Direct gene sequencing of K-ras gene including codon 12, 13 and 61 as well asthe mutation cluster region (MCR) of APC genewas performed.RESULTS K-ras gene mutation frequency inACF, adenoma and carcinoma was 17.6% (6/34), 13.3% (2/ 15), and 14.3% (5/ 35)respectively, showing no difference ( P > 0.05)in K-fas gene mutation among three pathologicprocedures. The K-ras gene mutation inadenoma, carcinoma and 4 ACF restricted incodon 12 (GGT→GAT), but the other 2 mutationsfrom ACF located in codon 13 (GGC→GAC). K-res gene mutation was found more frequently inolder patients and patients with polypoidcancer. No mutation in codon 61 was found in thethree tissue types. Mutation rate of APO gene inadenoma and carcinoma was 22.9% (8/35) and26.7% (4/ 15), which was higher than ACF(2.9%) (P < 0.05). APC gene mutation incarcinoma was not correlated with age ofpatients, location, size and differentiation oftumor.CONCLUSION ACF might be a very earlymorphological lesion in the tumorogenesis ofcolorectal tumor. The morphological feature andgene mutation status was different in ACF andadenoma. ACF is possibly putative'microadenoma' that might be the precursor ofadenoma. In addition, the development of asubgroup of colorectal carcinomas mightundergo a way of 'normal epithelium→ ACF→carcinomas'.展开更多
AIM:To evaluate the potential role of hyperreflective foci(HF) as a prognostic indicator of visual outcome in patients with macular edema(ME) due to retinal vein occlusion(RVO).METHODS:We retrospectively reviewed 50 e...AIM:To evaluate the potential role of hyperreflective foci(HF) as a prognostic indicator of visual outcome in patients with macular edema(ME) due to retinal vein occlusion(RVO).METHODS:We retrospectively reviewed 50 eyes of 50 patients with ME due to ischemic central retinal vein occlusion(CRVO),non-ischemic CRVO and branch retinal vein occlusion(BRVO) who were treated with anti-vascular endothelial growth factor(anti-VEGF) at Beijing Tongren Eye Center from January 2013 to July 2016.All patients underwent best-corrected visual acuity(BCVA),spectral domain optical coherence tomography(SD-OCT) at baseline and follow-up.Such factors were evaluated and compared among three groups as baseline and final BCVA,central retinal thickness(CRT),external limiting membrane(ELM) status and the numbers of HF in different position.Multiple linear regression analysis was employed to analyze the relationship between baseline HF and final BCVA.Changes of HF before and after treatment were evaluated too.RESULTS:Among three groups,HF could be located in each retinal layers,as well as in vitreous cavity.The mean HF in outer retinal layer(ORL) at baseline was 5.29±8.48 in ischemic CRVO with intact ELM,1.93±2.76 in non-ischemic CRVO,and 1.75±2.05 in BRVO.With disrupted ELM,the mean HF in ORL increased.There was statistically difference of HF in ORL between intact and disrupted ELM.The numbers of HF in ORL were associated with poor visual outcome among three groups.However,HF in inner retinal layer(IRL) and vitreous cavity were not associated with poor visual outcome.Meanwhile,the baseline HF in ORL and vitreous cavity reduced significantly in nonischemic CRVO and BRVO after anti-VEGF treatment.CONCLUSION:The numbers of HF in ORL are prognostic factors associated with the final BCVA in patients with ME due to RVO after anti-VEGF treatment.展开更多
AIM:To clarify the relationship of human rectal aberrant crypt foci and formation of colorectal polyp.METHODS:Eighty-nine subjects were recruited from the population of Japanese individuals who underwent polypectomy a...AIM:To clarify the relationship of human rectal aberrant crypt foci and formation of colorectal polyp.METHODS:Eighty-nine subjects were recruited from the population of Japanese individuals who underwent polypectomy at Yokohama City University Hospital.All patients had baseline adenomas removed at year 0 colonoscopy.Aberrant crypt foci(ACF) were defined as lesions in which the crypts were more darkly stained with methylene blue than normal crypts and had larger diameters,often with oval or slit-like lumens and a thicker epithelial lining.RESULTS:A total of 366 ACFs were identified in 89 patients;all had baseline adenomas removed at the first examination(year 0) colonoscopy and returned for the second(year 1).ACF in the lower rectum were assessed at year 0 and study group were divided into two groups depend on ACF numbers,0-3 or over 3.All participants were examined in the number and maximum size of adenoma.There was no statistical difference in number and maximum size of ACF at year 0,however,maximum size of adenoma was larger in over 3 group than 0-3 group at year 1.CONCLUSION:The number of ACF may be a predictive factor of relatively large adenoma incidence in the pilot phase study.展开更多
Dear Editor,We’re interested in the article by Mo and colleagues~[1] about"Evaluation of hyperreflective foci as a prognostic factor of visual outcome in retinal vein occlusion".They performed a multiple li...Dear Editor,We’re interested in the article by Mo and colleagues~[1] about"Evaluation of hyperreflective foci as a prognostic factor of visual outcome in retinal vein occlusion".They performed a multiple linear regression analysis with backward elimination to analyse the association of best corrected visual acuity(BCVA)with the numbers of hyperreflective foci(HF)in different layers.In addition,they summarized the results of multivariate regression analyses in Table 3~[1].展开更多
In this paper, we investigate the existence of local limit cycles obtained by perturbing degenerate and weak foci of two-dimensional cubic systems of differential equations. In particular, we consider a specific class...In this paper, we investigate the existence of local limit cycles obtained by perturbing degenerate and weak foci of two-dimensional cubic systems of differential equations. In particular, we consider a specific class of such systems where the origin is a degenerate focus. By utilizing a Liapunov function method and the stability results that follow, we first determine constraints on the system to maximize the number of local limit cycles that can be obtained by perturbing the degenerate focus at the origin. Once this is established, we add on the additional assumption that the system has a weak focus at , where , and determine conditions to maximize the number of additional local limit cycles that can be obtained near this fixed point. We will ultimately achieve an example of a cubic system with three local limit cycles about the degenerate focus and one local limit cycle about the weak focus.展开更多
Genetic and metabolic engineering approaches are powerful tools for improving the tolerance of maize to abiotic stresses because they are faster and can afford greater control over agronomically useful traits. However...Genetic and metabolic engineering approaches are powerful tools for improving the tolerance of maize to abiotic stresses because they are faster and can afford greater control over agronomically useful traits. However, in-depth understanding of the molecular mechanisms controlling response to abiotic stresses is the prerequisite for successful implementation of these strategies. A great flaw to dissect the biological mechanisms by genome sequencing is that genome sequencing approach could not reflect real-time molecular actions of plants especially under the stresses because the living organisms rarely live in unchanging environments. Post-genomics such as transcriptomics, metabolomics, and proteomics can generate knowledge that is closer to the biological processes. With the development of post-genomics, it can be expected that voluminous data will be generated. This paper proposes that future research on maize stress tolerance in the era of post-genomics should focus on metabolomics and proteomics; stress tolerance of whole plant rather than individual tissues or organs; coordination of expression of genes among tissues; characterization of promoters of stress-responsive genes; interrelation between mechanisms for tolerance to, and growth recovery from the stress; hexose metabolism as well as the glycolysis pathway; and foundation genotypes.展开更多
Background:Schistosoma mansoni,causing intestinal schistosomiasis,is widely distributed in Ethiopia and new transmission foci are continually reported.Here we report new transmission sites and prevalence ofS.mansoni i...Background:Schistosoma mansoni,causing intestinal schistosomiasis,is widely distributed in Ethiopia and new transmission foci are continually reported.Here we report new transmission sites and prevalence ofS.mansoni infection among school children in Yachi areas,southwestern Ethiopia.Methods:A cross-sectional survey was conducted among school children of Yachi Yisa and Yachi Efo elementary schools,southwestern Ethiopia,from April 2017 to June 2017.Three hundred seventeen school children aged six to 15 years were randomly selected to provide stool specimens for helminth infection examination by Kato-Katz and formol-ether concentration techniques.Snail survey was carried out to assess schistosome infection inBiomphalaria pfeifferi.Laboratory bred mice were also exposed to schistosome cercariae shed byB.pfeifferi en masse for definite identification ofSchistosoma species.Results:From the 317 stool specimens examined using double Kato-Katz thick smear and single formol-ether concentration techniques,224(70.7%)were found positive for at least one intestinal helminth species.The most prevalent parasite wasS.mansoni(42.9%)followed byTrichuris trichiura(34.1%)andAscaris lumbricoides(14.2%).The prevalence ofS.mansoni infection was significantly higher among the children attending Yachi Yisa School(49.4%)than those in Yachi Efo School(35.6%)(P=0.002).The study also revealed that there was a significantly higher prevalence ofS.mansoni infection among males(51.2%)than females(33.1%)(P<0.001).However,the prevalence ofS.mansoni infection was not significantly associated with age categories(P=0.839).B.pfeifferi snails infected with schistosomes were collected from the water bodies found in the study area.After six weeks post exposure,adultS.mansoni worms were harvested from the mesenteric veins of laboratory bred mice.Conclusions:The study revealed establishment of newS.mansoni transmission foci and moderate prevalence of schistosomiasis in Yachi areas.Hence,treatment of all school-age children once every two years is recommended.Snail control and non-specific control approaches including provision of clean water supply and health education should also complement mass drug administration of praziquantel.展开更多
The origin of SARS-CoV-2 is still an unresolved mystery.In this study,we systematically reviewed the main research progress of wild animals carrying virus highly homologous to SARS-CoV-2 and analyzed the natural foci ...The origin of SARS-CoV-2 is still an unresolved mystery.In this study,we systematically reviewed the main research progress of wild animals carrying virus highly homologous to SARS-CoV-2 and analyzed the natural foci characteristics of SARS-CoV-2.The complexity of SARS-CoV-2 origin in wild animals and the possibility of SARS-CoV-2 long-term existence in human populations are also discussed.The joint investigation of corona virus carried by wildlife,as well as the ecology and patho-ecology of bats and other wildlife,are key measures to further clarify the characteristics of natural foci of SARS-CoV-2 and actively defend against future outbreaks of emerging zoonotic diseases.展开更多
Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as ...Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as capillary occlusion, acellular capillaries and retinal non-perfusion, aggregate retinal ischemia and represent relatively late events in diabetic retinopathy. In fact, retinal microvascular injury is an early event in diabetic retinopathy involving multiple biochemical alterations, and is manifested by changes to the retinal neurovascular unit and its cellular components. Currently, intravitreal anti-vascular endothelial growth factor therapy is the firstline treatment for diabetic macular edema, and benefits the patient by decreasing the edema and improving visual acuity. However, a significant proportion of patients respond poorly to anti-vascular endothelial growth factor treatments, indicating that factors other than vascular endothelial growth factor are involved in the pathogenesis of diabetic macular edema. Accumulating evidence confirms that low-grade inflammation plays a critical role in the pathogenesis and development of diabetic retinopathy as multiple inflammatory factors, such as interleukin-1β, monocyte chemotactic protein-1 and tumor necrosis factor-α, are increased in the vitreous and retina of diabetic retinopathy patients. These inflammatory factors, together with growth factors such as vascular endothelial growth factor, contribute to blood-retinal barrier breakdown, vascular damage and neuroinflammation, as well as pathological angiogenesis in diabetic retinopathy, complicated by diabetic macular edema and proliferative diabetic retinopathy. In addition, retinal cell types including microglia, Müller glia, astrocytes, retinal pigment epithelial cells, and others are activated, to secrete inflammatory mediators, aggravating cell apoptosis and subsequent vascular leakage. New therapies, targeting these inflammatory molecules or related signaling pathways, have the potential to inhibit retinal inflammation and prevent diabetic retinopathy progression. Here, we review the relevant literature to date, summarize the inflammatory mechanisms underlying the pathogenesis of diabetic retinopathy, and propose inflammation-based treatments for diabetic retinopathy and diabetic macular edema.展开更多
基金This subject is supported by the Fund for Returned Scientists and Scholars,[1999]363.Chinese Ministry of Education.
文摘AIM To study the genetic alteration in ACF andto define the possibility that ACF may be a veryearly morphological lesion with molecularchanges, and to explore the relationshipbetween ACF and colorectal adenoma evencarcinoma.METHODS DNA from 35 CRC, 15 adenomas, 34ACF and 10 normal mucus was isolated by meansof microdissection. Direct gene sequencing of K-ras gene including codon 12, 13 and 61 as well asthe mutation cluster region (MCR) of APC genewas performed.RESULTS K-ras gene mutation frequency inACF, adenoma and carcinoma was 17.6% (6/34), 13.3% (2/ 15), and 14.3% (5/ 35)respectively, showing no difference ( P > 0.05)in K-fas gene mutation among three pathologicprocedures. The K-ras gene mutation inadenoma, carcinoma and 4 ACF restricted incodon 12 (GGT→GAT), but the other 2 mutationsfrom ACF located in codon 13 (GGC→GAC). K-res gene mutation was found more frequently inolder patients and patients with polypoidcancer. No mutation in codon 61 was found in thethree tissue types. Mutation rate of APO gene inadenoma and carcinoma was 22.9% (8/35) and26.7% (4/ 15), which was higher than ACF(2.9%) (P < 0.05). APC gene mutation incarcinoma was not correlated with age ofpatients, location, size and differentiation oftumor.CONCLUSION ACF might be a very earlymorphological lesion in the tumorogenesis ofcolorectal tumor. The morphological feature andgene mutation status was different in ACF andadenoma. ACF is possibly putative'microadenoma' that might be the precursor ofadenoma. In addition, the development of asubgroup of colorectal carcinomas mightundergo a way of 'normal epithelium→ ACF→carcinomas'.
文摘AIM:To evaluate the potential role of hyperreflective foci(HF) as a prognostic indicator of visual outcome in patients with macular edema(ME) due to retinal vein occlusion(RVO).METHODS:We retrospectively reviewed 50 eyes of 50 patients with ME due to ischemic central retinal vein occlusion(CRVO),non-ischemic CRVO and branch retinal vein occlusion(BRVO) who were treated with anti-vascular endothelial growth factor(anti-VEGF) at Beijing Tongren Eye Center from January 2013 to July 2016.All patients underwent best-corrected visual acuity(BCVA),spectral domain optical coherence tomography(SD-OCT) at baseline and follow-up.Such factors were evaluated and compared among three groups as baseline and final BCVA,central retinal thickness(CRT),external limiting membrane(ELM) status and the numbers of HF in different position.Multiple linear regression analysis was employed to analyze the relationship between baseline HF and final BCVA.Changes of HF before and after treatment were evaluated too.RESULTS:Among three groups,HF could be located in each retinal layers,as well as in vitreous cavity.The mean HF in outer retinal layer(ORL) at baseline was 5.29±8.48 in ischemic CRVO with intact ELM,1.93±2.76 in non-ischemic CRVO,and 1.75±2.05 in BRVO.With disrupted ELM,the mean HF in ORL increased.There was statistically difference of HF in ORL between intact and disrupted ELM.The numbers of HF in ORL were associated with poor visual outcome among three groups.However,HF in inner retinal layer(IRL) and vitreous cavity were not associated with poor visual outcome.Meanwhile,the baseline HF in ORL and vitreous cavity reduced significantly in nonischemic CRVO and BRVO after anti-VEGF treatment.CONCLUSION:The numbers of HF in ORL are prognostic factors associated with the final BCVA in patients with ME due to RVO after anti-VEGF treatment.
基金Supported by Grant-in-Aid for Research on the Third Term Comprehensive Control Research for Cancer from the Ministry of Health,Labour and Welfare,Japan to Nakajima Aa grant from the National Institute of Biomedical Innovation (NBIO) to Nakajima Aa grant from the Ministry of Education,Culture,Sports,Science and Technology,Japan (KIBAN-B) to Nakajima A and (KIBAN-C) to Takahashi H
文摘AIM:To clarify the relationship of human rectal aberrant crypt foci and formation of colorectal polyp.METHODS:Eighty-nine subjects were recruited from the population of Japanese individuals who underwent polypectomy at Yokohama City University Hospital.All patients had baseline adenomas removed at year 0 colonoscopy.Aberrant crypt foci(ACF) were defined as lesions in which the crypts were more darkly stained with methylene blue than normal crypts and had larger diameters,often with oval or slit-like lumens and a thicker epithelial lining.RESULTS:A total of 366 ACFs were identified in 89 patients;all had baseline adenomas removed at the first examination(year 0) colonoscopy and returned for the second(year 1).ACF in the lower rectum were assessed at year 0 and study group were divided into two groups depend on ACF numbers,0-3 or over 3.All participants were examined in the number and maximum size of adenoma.There was no statistical difference in number and maximum size of ACF at year 0,however,maximum size of adenoma was larger in over 3 group than 0-3 group at year 1.CONCLUSION:The number of ACF may be a predictive factor of relatively large adenoma incidence in the pilot phase study.
文摘Dear Editor,We’re interested in the article by Mo and colleagues~[1] about"Evaluation of hyperreflective foci as a prognostic factor of visual outcome in retinal vein occlusion".They performed a multiple linear regression analysis with backward elimination to analyse the association of best corrected visual acuity(BCVA)with the numbers of hyperreflective foci(HF)in different layers.In addition,they summarized the results of multivariate regression analyses in Table 3~[1].
文摘In this paper, we investigate the existence of local limit cycles obtained by perturbing degenerate and weak foci of two-dimensional cubic systems of differential equations. In particular, we consider a specific class of such systems where the origin is a degenerate focus. By utilizing a Liapunov function method and the stability results that follow, we first determine constraints on the system to maximize the number of local limit cycles that can be obtained by perturbing the degenerate focus at the origin. Once this is established, we add on the additional assumption that the system has a weak focus at , where , and determine conditions to maximize the number of additional local limit cycles that can be obtained near this fixed point. We will ultimately achieve an example of a cubic system with three local limit cycles about the degenerate focus and one local limit cycle about the weak focus.
基金supported by the National Basic Research Program of China(2011CB100100)the 948 Program from the Ministry of Agriculture of China (2001-205)+2 种基金the Development Programs for Guangxi Science and Technology Research, China(Guikegong 10100005-4 and 0228019-6)the Key Laboratory of Ministry of Education for Microbial and Plant Genetic Engineering, China (Director’s grant-06-11)the Opening Project of Guangxi Key Laboratory of Subtropical Bioresource Conservation and Utilization, China (SB0601)
文摘Genetic and metabolic engineering approaches are powerful tools for improving the tolerance of maize to abiotic stresses because they are faster and can afford greater control over agronomically useful traits. However, in-depth understanding of the molecular mechanisms controlling response to abiotic stresses is the prerequisite for successful implementation of these strategies. A great flaw to dissect the biological mechanisms by genome sequencing is that genome sequencing approach could not reflect real-time molecular actions of plants especially under the stresses because the living organisms rarely live in unchanging environments. Post-genomics such as transcriptomics, metabolomics, and proteomics can generate knowledge that is closer to the biological processes. With the development of post-genomics, it can be expected that voluminous data will be generated. This paper proposes that future research on maize stress tolerance in the era of post-genomics should focus on metabolomics and proteomics; stress tolerance of whole plant rather than individual tissues or organs; coordination of expression of genes among tissues; characterization of promoters of stress-responsive genes; interrelation between mechanisms for tolerance to, and growth recovery from the stress; hexose metabolism as well as the glycolysis pathway; and foundation genotypes.
基金We sincerely thank the School of Graduate Studies,Addis Ababa University for financial support.
文摘Background:Schistosoma mansoni,causing intestinal schistosomiasis,is widely distributed in Ethiopia and new transmission foci are continually reported.Here we report new transmission sites and prevalence ofS.mansoni infection among school children in Yachi areas,southwestern Ethiopia.Methods:A cross-sectional survey was conducted among school children of Yachi Yisa and Yachi Efo elementary schools,southwestern Ethiopia,from April 2017 to June 2017.Three hundred seventeen school children aged six to 15 years were randomly selected to provide stool specimens for helminth infection examination by Kato-Katz and formol-ether concentration techniques.Snail survey was carried out to assess schistosome infection inBiomphalaria pfeifferi.Laboratory bred mice were also exposed to schistosome cercariae shed byB.pfeifferi en masse for definite identification ofSchistosoma species.Results:From the 317 stool specimens examined using double Kato-Katz thick smear and single formol-ether concentration techniques,224(70.7%)were found positive for at least one intestinal helminth species.The most prevalent parasite wasS.mansoni(42.9%)followed byTrichuris trichiura(34.1%)andAscaris lumbricoides(14.2%).The prevalence ofS.mansoni infection was significantly higher among the children attending Yachi Yisa School(49.4%)than those in Yachi Efo School(35.6%)(P=0.002).The study also revealed that there was a significantly higher prevalence ofS.mansoni infection among males(51.2%)than females(33.1%)(P<0.001).However,the prevalence ofS.mansoni infection was not significantly associated with age categories(P=0.839).B.pfeifferi snails infected with schistosomes were collected from the water bodies found in the study area.After six weeks post exposure,adultS.mansoni worms were harvested from the mesenteric veins of laboratory bred mice.Conclusions:The study revealed establishment of newS.mansoni transmission foci and moderate prevalence of schistosomiasis in Yachi areas.Hence,treatment of all school-age children once every two years is recommended.Snail control and non-specific control approaches including provision of clean water supply and health education should also complement mass drug administration of praziquantel.
基金This work was supported by the State Key Research Development Program of China(2019YFC1200601,2019YFC1200500,2019YFC1200700).
文摘The origin of SARS-CoV-2 is still an unresolved mystery.In this study,we systematically reviewed the main research progress of wild animals carrying virus highly homologous to SARS-CoV-2 and analyzed the natural foci characteristics of SARS-CoV-2.The complexity of SARS-CoV-2 origin in wild animals and the possibility of SARS-CoV-2 long-term existence in human populations are also discussed.The joint investigation of corona virus carried by wildlife,as well as the ecology and patho-ecology of bats and other wildlife,are key measures to further clarify the characteristics of natural foci of SARS-CoV-2 and actively defend against future outbreaks of emerging zoonotic diseases.
基金supported by the National Natural Science Foundation of China,No. 82171062 (to JFZ)。
文摘Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as capillary occlusion, acellular capillaries and retinal non-perfusion, aggregate retinal ischemia and represent relatively late events in diabetic retinopathy. In fact, retinal microvascular injury is an early event in diabetic retinopathy involving multiple biochemical alterations, and is manifested by changes to the retinal neurovascular unit and its cellular components. Currently, intravitreal anti-vascular endothelial growth factor therapy is the firstline treatment for diabetic macular edema, and benefits the patient by decreasing the edema and improving visual acuity. However, a significant proportion of patients respond poorly to anti-vascular endothelial growth factor treatments, indicating that factors other than vascular endothelial growth factor are involved in the pathogenesis of diabetic macular edema. Accumulating evidence confirms that low-grade inflammation plays a critical role in the pathogenesis and development of diabetic retinopathy as multiple inflammatory factors, such as interleukin-1β, monocyte chemotactic protein-1 and tumor necrosis factor-α, are increased in the vitreous and retina of diabetic retinopathy patients. These inflammatory factors, together with growth factors such as vascular endothelial growth factor, contribute to blood-retinal barrier breakdown, vascular damage and neuroinflammation, as well as pathological angiogenesis in diabetic retinopathy, complicated by diabetic macular edema and proliferative diabetic retinopathy. In addition, retinal cell types including microglia, Müller glia, astrocytes, retinal pigment epithelial cells, and others are activated, to secrete inflammatory mediators, aggravating cell apoptosis and subsequent vascular leakage. New therapies, targeting these inflammatory molecules or related signaling pathways, have the potential to inhibit retinal inflammation and prevent diabetic retinopathy progression. Here, we review the relevant literature to date, summarize the inflammatory mechanisms underlying the pathogenesis of diabetic retinopathy, and propose inflammation-based treatments for diabetic retinopathy and diabetic macular edema.
